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Updated: Oct 11, 2025

Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution
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Targeting ACC for NASH resolution.

Xiao-Jing Zhang1, Jingjing Cai2, Hongliang Li3

  • 1Department of Cardiology, Renmin Hospital; School of Basic Medical Science, Wuhan University, Wuhan 430071, China; Institute of Model Animal of Wuhan University, Wuhan 430071, China.

Trends in Molecular Medicine
|November 30, 2021
PubMed
Summary
This summary is machine-generated.

Acetyl-CoA carboxylase (ACC) 1/2 inhibitors show promise for nonalcoholic steatohepatitis (NASH). Co-administration with a DGAT2 inhibitor mitigated associated hyperlipidemia, improving therapeutic potential.

Keywords:
ACCDGAT2NASHhepatic steatosishypertriglyceridemia

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Area of Science:

  • Metabolic diseases
  • Hepatology
  • Pharmacology

Background:

  • Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with limited treatment options.
  • Acetyl-CoA carboxylase (ACC) 1/2 inhibitors are being investigated for their potential to treat NASH.
  • ACC inhibition can lead to hyperlipidemia, a potential side effect that requires management.

Purpose of the Study:

  • To evaluate the efficacy of ACC 1/2 inhibitors in treating NASH.
  • To investigate the impact of co-administering ACC 1/2 inhibitors with diacylglycerol acyltransferase 2 (DGAT2) inhibitors on NASH and associated metabolic changes.

Main Methods:

  • Utilized ACC 1/2 inhibitors as monotherapy for NASH treatment.
  • Employed co-administration of ACC 1/2 inhibitors and DGAT2 inhibitors in a study cohort.
  • Monitored liver steatosis and serum triglyceride levels as key outcome measures.

Main Results:

  • Monotherapy with ACC 1/2 inhibitors significantly reduced liver steatosis.
  • ACC 1/2 inhibitor monotherapy led to an increase in serum triglycerides (hyperlipidemia).
  • Co-administration with a DGAT2 inhibitor effectively mitigated the hyperlipidemic side effect induced by ACC 1/2 inhibitors.

Conclusions:

  • ACC 1/2 inhibitors demonstrate anti-NASH potential by reducing liver fat.
  • Combining ACC 1/2 inhibitors with DGAT2 inhibitors offers a strategy to manage NASH while preventing treatment-induced hyperlipidemia.